Multi-gene testing in neurological disorders showed an improved diagnostic yield: data from over 1000 Indian patients.

Child Child, Preschool Cohort Studies Data Analysis Female Genetic Predisposition to Disease / epidemiology Genetic Testing / methods High-Throughput Nucleotide Sequencing / methods Humans India / epidemiology Male Multifactorial Inheritance / genetics Mutation / genetics Nervous System Diseases / diagnosis

Genetic testing Multi-gene panel Neurological disorders Next-generation sequencing

Journal

Journal of neurology

ISSN: 1432-1459

Titre abrégé: J Neurol

Pays: Germany

ID NLM: 0423161

Informations de publication

Date de publication:
Aug 2019

Historique:

received: 21 01 2019

accepted: 03 05 2019

revised: 25 04 2019

pubmed: 10 5 2019

medline: 10 1 2020

entrez: 10 5 2019

Statut: ppublish

Résumé

Neurological disorders are clinically heterogeneous group of disorders and are major causes of disability and death. Several of these disorders are caused due to genetic aberration. A precise and confirmatory diagnosis in the patients in a timely manner is essential for appropriate therapeutic and management strategies. Due to the complexity of the clinical presentations across various neurological disorders, arriving at an accurate diagnosis remains a challenge. We sequenced 1012 unrelated patients from India with suspected neurological disorders, using TruSight One panel. Genetic variations were identified using the Strand NGS software and interpreted using the StrandOmics platform. We were able to detect mutations in 197 genes in 405 (40%) cases and 178 mutations were novel. The highest diagnostic rate was observed among patients with muscular dystrophy (64%) followed by leukodystrophy and ataxia (43%, each). In our cohort, 26% of the patients who received definitive diagnosis were primarily referred with complex neurological phenotypes with no suggestive diagnosis. In terms of mutations types, 62.8% were truncating and in addition, 13.4% were structural variants, which are also likely to cause loss of function. In our study, we observed an improved performance of multi-gene panel testing, with an overall diagnostic yield of 40%. Furthermore, we show that NGS (next-generation sequencing)-based testing is comprehensive and can detect all types of variants including structural variants. It can be considered as a single-platform genetic test for neurological disorders that can provide a swift and definitive diagnosis in a cost-effective manner.

Sections du résumé

BACKGROUND BACKGROUND

METHODS METHODS

We sequenced 1012 unrelated patients from India with suspected neurological disorders, using TruSight One panel. Genetic variations were identified using the Strand NGS software and interpreted using the StrandOmics platform.

RESULTS RESULTS

We were able to detect mutations in 197 genes in 405 (40%) cases and 178 mutations were novel. The highest diagnostic rate was observed among patients with muscular dystrophy (64%) followed by leukodystrophy and ataxia (43%, each). In our cohort, 26% of the patients who received definitive diagnosis were primarily referred with complex neurological phenotypes with no suggestive diagnosis. In terms of mutations types, 62.8% were truncating and in addition, 13.4% were structural variants, which are also likely to cause loss of function.

CONCLUSION CONCLUSIONS

In our study, we observed an improved performance of multi-gene panel testing, with an overall diagnostic yield of 40%. Furthermore, we show that NGS (next-generation sequencing)-based testing is comprehensive and can detect all types of variants including structural variants. It can be considered as a single-platform genetic test for neurological disorders that can provide a swift and definitive diagnosis in a cost-effective manner.

Identifiants

DOI: 10.1007/s00415-019-09358-1 PMID: 31069529

pubmed: 31069529

doi: 10.1007/s00415-019-09358-1

pii: 10.1007/s00415-019-09358-1

doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

1919-1926

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